Breast cancer, DPYD mutations and capecitabine-related ileitis: description of two cases and a review of the literature

Abstract

Despite many treatment advances, metastatic breast cancer remains an incurable disease and is the third leading cause of cancer-related deaths in Europe. Capecitabine has become a standard treatment option for metastatic breast cancer, as a single agent or in combination. Hand-foot syndrome and diarrhoea are the most frequently reported side effects, while capecitabine-related ileitis is very rare. Deficiency of dihydropyrimidine dehydrogenase activity leads to severe toxicities after administration of 5-fluorouracil or its prodrugs. We report two cases of patients with metastatic breast cancer who developed ileitis after treatment with capecitabine. One patient had a DPYD gene abnormality.

Capecitabine-Associated Terminal Ileitis

“…In the current case, the complaints of diarrhea started within 2 weeks after the first administration of chemotherapy and worsened over time, needing further diagnostic tests, which revealed a terminal ileitis. Terminal ileitis has been previously reported in 8 cases (Table 1 ) [ 6 , 7 , 8 , 9 , 10 , 11 ]. Yet, the pathophysiology and the management of capecitabine-induced terminal ileitis remain unclear.…”

Capecitabine-Induced Enterocolitis

“…5-FU, the drug’s active metabolite, has also been reported to result in coronary artery vasospasm and may therefore lead to ischemia due to endothelial damage of intestinal vasculature [ 6 , 15 ]. Furthermore, mutations in DPYD, which codes for dihydropyrimidine dehydrogenase, have been previously associated with severe adverse reactions to capecitabine, including ileitis and cytomegalovirus-associated enterocolitis [ 16 , 17 ]. Hence, several medical associations recommend that all patients undergoing treatment with 5-FU drugs and prodrugs be tested for DPYD mutations [ 18 ].…”

Capecitabine-Induced Terminal Ileitis: Case Report and Literature Review

“…In both cases, there was only a partial reduction in DPD activity. Curiously, the patient described by Mokrim et al only developed symptoms of ileitis after completing an entire cycle of capecitabine despite having diminished DPD activity [ 10 ]. Recommendations are in place advocating for routing screening for four most common DPD variants before initiating treatment with capecitabine, especially in regions with accentuated prevalence [ 19 ].…”